Functional Lymphoid Anatomy Flashcards
Name 5 sites of secondary/peripheral lymphoid tissue
Adenoids Tonsils Lymph Nodes Peyer's patches (mucosal tissue) spleen
Name the two central/primary lymphoid tissues
Bone marrow
Thymus
What occurs in central vs peripheral lymphoid tissues?
Central: generates B and T cells, responsible for central tolerance
Peripheral: Primes B and T cells into effector cells (supports circulating lymphocyte survival, peripheral tolerance, activation of naive T cells)
Where do B cells and T cells originate? What are they derived from?
Bone Marrow- all lymphocytes are derived from hematopoietic stem cells.
What are stromal cells?
Stromal cells (in the bone marrow) provide critical signals (cytokines) that direct the developmental program of the progenitor cells and eventually b-cells
ie. they are critical for B-cell development
Where do the final stages of development of B cells occur (from naive to effector cells)
Peripheral lymphoid organs
What is central tolerance for B cells?
Immature B cells in the bone marrow are tested for reactivity to self antigens, or autoreactivity, and are eliminated (apoptosis) if they are autoreactive.
Immature B cells that have no strong reactivity to self are allowed to mature
What happens to immature B cells that are not self-reactive? Where do they go next?
Immature B cells that have no strong reactivity to self are allowed to mature. They leave the marrow via sinusoids that enter the central sinus and are carried by the venous blood supply to the spleen
What is the fate of a B cell that reacts to multi-valent self molecules?
1) Rescue by receptor editing -or-
2) Death via apoptosis
What is the fate of a B cell that reacts to soluble self-molecule?
Migrates to the periphery but becomes anergic
What is the fate of a B cell that reacts with low affinity to soluble self molecule (no cross linking occurs)
Migrates to the periphery as an autoreactive cell
Germinal centers and lymphoid follicles are unique to what class of lymphoid organs (central or peripheral)?
Peripheral only
What cells are found in the cortex of the thymus?
Immature thymocytes and scattered macrophages
What cells are found in the medulla of the thymus?
more mature thymocytes (single positive), dendritic cells and macrophages
What is the fate of 98% of thymocytes?
Death by apoptosis and removal by cortical macrophages
What survival factor is required for the survival of thymocytes in the thymus?
IL-7, secreted by cortical epithelial cells.
In the absence of IL-7, thymocytes will die
Describe the rate of production of new T cells in the thymus throughout a persons’ lifetime
The development of new T cells in the thymus slows down in mature individuals.
The development of new T cells is greatest before puberty
How are T cells numbers maintained throughout a person’s life if the generation of new T cells in the thymus slows down?
1) Long-lived individual T cells
2) Division of mature T cells outside the central lymphoid tissue
Where does most of the T cell development occur?
thymic cortex
What occurs at the corticomedullary junction of the thymus?
T cell progenitors enter
Describe the thymic cortical stroma
Network of epithelia where the T cell precursors reside; provides unique microenvironment for T cell development (like B cell stromal cells); has epithelial cells with long branching processes that express both MHC Class I and II molecules on their surface.
T cell development:
Where do T cell progenitors from the bone marrow enter the thymus? Where do the cells go within the thymus?
Progenitors from the bone marrow enter at the corticomedullary junction and migrate to the outer cortex
T cell development:
Following entry into the thymus, what happens to cells at the outer cortex/subcapsular region of the thymus?
Large immature double-negative thymocytes proliferate vigorously
What are markers are double-negative T cells missing?
T-Cell Receptor complex: CD3
T cell Co-receptor: CD4 and CD8
Proliferating thymocytes from the outer cortex migrate deeper into the cortex in order to undergo what process?
Receptor rearrangement until they become CD3+ and CD4+CD8+ double positive thymocytes
Describe positive selection of double positive thymocytes.
If the double positive T cell does recognize self-peptide: self-MHC complexes, then it will drop one of the co-receptors and become either CD3+CD4+ or CD3+CD8+ single positive T cells and migrate to the periphery
Describe negative selection of double positive thymocytes.
If the single positive T cell recognizes self peptides: self-MHC too strongly, then it will undergo apoptosis.
If it does not, it will be exported to the periphery
After maturation, what happens to the T cells?
Both CD4+ and CD8+ T cells will circulate in the bloodstream and mature naive lymphocytes
Progression of T cell development in the thymus is dependent on what?
Timely expression of various surface and signaling molecules
What type of lymphocytes are continually recirculating through peripheral lymphoid tissue?
Mature, naive lymphocytes- they are looking to encounter pathogen antigens which have been carried there from sites of infection
Through what structures do lymphocytes enter the peripheral lymphoid tissue?
Artery –> High Endothelial Venules (HEVs) and enter the paracortical area
Cytokines draw them in
How does antigen enter peripheral lymphoid tissue?
Through the afferent lymphatics
What is the primary cell type of the paracortical region of the lymph node?
T-cells
What two ways can antigen reach T cells?
Antigens freely float, or are actively brought by APCs to the lymph node driven by cytokines
How does freely floating Ag get presented to T and B cells in the lymph node?
Antigen capture: opsonized antigen enters the lymph node via afferent lymphatics –> binds to compliment receptors on the surface of macrophages (of subscapular sinus- special, they don’t destroy antigen, preserve it and pass it on to FDC or show to B cells directly) –> trapped antigen encountered by B cell, or, –> antigen transported to follicular dc and localized on the surface of the FDC
Discuss briefly the process of B and T cell activation in lymph nodes
1) Naive B cells and CD4+ T cells recognize their antigen in the lymph node
2) Activated lymph nodes migrate towards each other via cytokines
3) B cells proliferation and differentiate,
4) Extrafollicular B cells re-stimulated by extrafollicular T cells to form short-lived plasma cells
5) Follicular B cells undergo somatic hypermutation, switching and formation of long-lived plasma and memory B cells
What is the purpose of the short lived plasma cells generated in the lymph nodes?
Quickly produce Ab to help ramp up the immune response to an invading pathogen
What process occurs in the germinal centers of lymph nodes?
B cells undergo intense proliferation and differentiation into plasma cells with the help of T helper cells
Differentiate a primary from secondary follicle in the lymph node
primary: darker, no activation of B cells
Secondary: Lighter- intense proliferation and differentiation of B cells
Is the spleen directly connected with the lymphatic system?
No
What types of infections does the spleen deal with?
The spleen is involved in immune responses to blood-borne pathogens (not tissues)
The spleen collects Ag from the blood
What is the secondary function of the spleen (non-immune)
Removal and disposal of red blood cells
Differentiate the red pulp from the white pulp of the spleen
Red pulp: majority of the spleen- sites of red blood disposal + iron recycling
White pulp: lymphocytes surrounding the arterioles running through the spleen –> immune responses to blood-borne pathogens
The spleen is especially good at clearing what type of bacterial infections? Give two examples of specific bacteria cleared by the spleen
Infections with encapsulated bacteria such as pneumococci and meningococci
What is in the periarteriolar lymphoid sheath (PALS) of the spleen?
The sheath of lymphocytes around a central arteriole; mainly T cells are found here
What are in the follicles of the spleen?
B cells- they may be germinal centers like in the lymph nodes
What are the marginal zones of the spleen?
The marginal zone surrounds the follicle, contains macrophages and resident, non-circulating B cells
Describe peripheral tolerance
Under the absence of infection, mature T and B cells that encounter a strongly cross-linking antigen in a secondary lymphoid organ will undergo anergy or apoptosis
What is MALT?
Mucosal lymphoid tissue
MALT comprises the body surfaces lined by mucus-secreting epithelium (GI tract, upper and lower respiratory tract, UG tract) and includes the exocrine glands associated with these tissues (lacrimal glands, salivary glands, lactating breast)
What is GALT?
Gut lymphoid tissue
What is the tolerance that must be acquired for GALT tissue?
Tolerance to food antigens and commensal bacteria
Describe the surface area of GALT
enormous
What are the special peripheral immune organs of GALT called?
Peyer’s patches
What are M cells?
Microfold cells (found in Peyer’s patches): specialized epithelial cells which directly collects antigen from lumen (luminal antigen sampling)
What are the follicles of peyer’s patches responsible for?
Follicles are large central domes of B cells, surrounded by smaller numbers of T cells
What cells are responsible for presenting antigen to T cells in peyer’s patches?
resident dendritic cells
What is the primary antibody type produced by B cells in MALT tissues/
IgA
Which cells produce defensin?
Paneth cells
What is BALT?
Bronchus/respiratory mucosal lymphoid tissue
